Prevention Of Perinatal Transmission In HBV-Infected Pregnant Women And Its Relationship To Susceptibility

Hepatitis B virus infection(HBV)is a major public health problem worldwide.Chronic hepatitis B(CHB)infection can lead to liver failure,cirrhosis and hepatocellular carcinoma,which seriously threat public health.There were 650000 people died from HBV related diseases.The routes of transmission of HBV mainly include mother to child transmission(MTCT),blood transmission and sexual transmission.Among which,MTCT is the most important transmission route in our country,30-50% HBV infection were through MTCT in other countries.Despite the administration of hepatitis B immune globulin(HBIG)and hepatitis B vaccines after birth,6% to 20% of infants still have a risk of HBV infection.In recent years,by using nucleos(t)ide analogues(NUCs)including lamivudine(LAM),telbivudine(LdT)and tenofovir disoproxil fumarate(TDF)in CHB infected pregnant women,MTCT prevention has been reported to be successful.To evaluated the efficacy and safety of LdT and TDF in HBe Ag-positive pregnant women.The 338 HBe Ag-positive pregnant women with HBV DNA>106 IU/m L enrolled were treated with antiviral therapy from 20-38 weeks of gestation(311 in LdT,27 in TDF).180 cases who were unwilling to take antiviral drugs served as controls.At present,Na+-taurochaolate cotransporting polypeptide(NTCP)also known as SLC10A1,encoded by the gene SLC10A1,was confirmed to be a functional receptor for HBV infection.Previous studies have indicated that SLC10A1 single gene polymorphism(SNP)variation is associated with susceptibility to HBV.However,previous studies on the host susceptibility to HBV infection have some limitations as neglecting the influence of the environment and the infection pathway.Therefore,our study which was based on MTCT will provide us a new clue to understand the mechanism of HBV infection and development of new drugs.In our study,we were aimed to identify SLC10A1 mutations(rs2296651(p.Ser267Phe),rs140189034(p.Val166Phe),rs202018997(p.Ala64Thr),rs61745930(p.Ile223Thr),rs72547506(p.Lys314Glu),rs72547507(p.Ile279Thr),rs201339654(p.Gly158Ser),rs36115704(c.356+1098C > T),rs10459536(c.5683169 A > C),rs7154439(c.-1956G>A))in HBV functional receptor associated with susceptibility to HBV infection by MTCT.A total of 421 individuals born from HBe Ag positive pregnant women with high load HBV DNA were included in our study,including 247 HBV-infected cases(NUCs(-)immunization(+)group 55 and NUCs(-)immunization(-)group 192)and 174 non-HBV-infected ones(NUCs(-)immunization(-)group 56 and NUCs(+)immunization(+)group 118).All recruiters were successfully and generally collected clinical data and blood sample,DNA extracted and genotyped.Then we performed a genetic case-control study.The main results are listed as follows:1.Maternal viral load decreased from 7.34 log10 IU/m L at baseline to 3.15 log10 IU/m L when delivery in LdT group.Similarly,maternal viral load decreased from 7.40 log10 IU/m L to 3.81 log10 IU/m L in TDF group.While in the control group,the HBV DNA levels did not change significantly.2.The earlier started the antiviral therapy,the more maternal viral load decreased.The HBV DNA levels just before delivery of LdT 20-27,LdT 28-32,LdT>33 groups were 1.61 log10 IU/m L,3.17 log10 IU/m L and 4.14 log10 IU/m L respectively.3.The incidence of undetectable cord blood HBV DNA levels of control groups was significant lower then treated group(LdT 20-27,11/11(100%),LdT 28-32,186/188(98.9%),LdT>33,8/8(100%),TDF group,23/23(100),control group,80/130(61.5%),P<0.05).4.The rate of HBs Ag positive in infants at 6 months between LdT/TDF group and control group(0% vs 15.3%),had significant difference(P<0.05).The rate of undetectable cord blood HBV DNA or HBs Ag negative in infants at 6 months was 100% in LdT/TDF group(LdT 20-27,26/26,LdT 28-32,270/270,LdT>33,22/22,TDF group,23/23),while the control group was 86.5%,which was of statistical significance(P<0.05).5.Among the treated groups,the incidence of vaginal delivery were 50%,44.5%,48% and 44.4% in LdT 20-27,LdT 28-32,LdT>33 and TDF group respectively,61.5%,39.4%,48%,11.1% infants of each group were feed with breastfeed.No severe adverse events observed or new infection happened among these infants.6.The differences of CK kinetics between LdT treated mothers or infants and control group had no significance(P>0.05).CK levels of LdT group and control group in age of 6 months-1 year were higher than age of 1-3 years(146.08 IU/L,170.8 IU/L vs 127.67 IU/L,139.5 IU/L).The CK levels of infants were higher than adults(baseline level of CK in mothers were 52.17-68.99 IU / L).7.There was one infant in LdT 28-32 group with negative HBs Ag at 6 months,but turned out to be HBs Ag positive(9.02 IU/ml)at 3 years old.After 3 month of Entecavir therapy(0.25 mg daily),his HBs Ag and HBV DNA replication level turned out to be negative,with anti-HBs 85.16IU/ml.8.There were no mutations detected among rs140189034,rs202018997,rs61745930,rs72547506,rs72547507,rs201339654 in our study.9.There were mutations detected among rs2296651,rs36115704,rs10459536,rs7154439.But the difference of distribution of the genotype frequency between HBV-infected ones(NUCs(-)immunization(+))and non-infected ones(NUCs(-)immunization(+))was not statistical significant(P>0.05).Conclusions:1.Both LdT/TDF have showed excellent efficacy and safety profile in high viral load pregnant women and their infants,and meanwhile they were associated with significant reduction of MTCT.2.The appropriate timing for treatment with LdT/TDF is 28-32 w,but not until 38 w is still worth trying rescue therapy.3.After NUCs combined with active and passive immunization,Spontaneous delivery and breastfeeding did not increase the risk of HBV infection.4.Short term application of LdT will not cause a significant increase of CK in maternal and infants.5.Horizontal transmission and infection may happen occasionally,particularly in vaccination failed child.6.There was no significant association between the SLC10A1 genetic variations and the susceptibility to HBV infection by the MTCT.